| 51. |
- Ekeblad, Sara, et al.
(författare)
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Gastrointestinal stromal tumors express the orexigen ghrelin
- 2006
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Ingår i: Endocrine-related cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 13:3, s. 963-70
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Tidskriftsartikel (refereegranskat)abstract
- Expression of the neuroendocrine marker synaptic vesicle protein 2 (SV2) has been reported in a few cases of gastrointestinal stromal tumors (GISTs). The goal of the present study was to assess the relevance of this finding and identify a possible hormone production in these tumors. We chose to study the orexigen ghrelin and its receptor, since these patients are seldom cachexic, even in advanced disease stages. We investigated ghrelin expression by means of immunohistochemistry on frozen or paraffin-embedded sections from 22 GISTs from a well-characterized patient material. Expression of the growth hormone secretagogue receptor, the ghrelin receptor, was investigated in a subset of lesions. In six tumors, mRNA levels of ghrelin, the ghrelin receptor, and SV2 were analyzed by real-time quantitative PCR. Totally 17 out of 22 tumors showed immunoreactivity for ghrelin. Five out of ten tumors were immunoreactive for the ghrelin receptor, and all of these co-expressed ghrelin. All tumors expressed ghrelin, ghrelin receptor, and SV2 mRNA. GISTs frequently express SV2, ghrelin, and its receptor, indicating the presence of autocrine/paracrine loops.
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| 52. |
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| 53. |
- Fjälling, M, et al.
(författare)
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Systemic radionuclide therapy using indium-111-DTPA-D-Phe1-octreotide in midgut carcinoid syndrome.
- 1996
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 37:9, s. 1519-21
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Tidskriftsartikel (refereegranskat)abstract
- A 55-yr-old woman with a midgut carcinoid syndrome due to metastatic spread of an ileal tumor to the liver, paraortic and mediastinal lymph nodes and to the skeleton was given systemic radionuclide therapy with 111In-DTPA-D-Phe1-octreotide. Before therapy, dosimetric calculations were performed on whole-body scintigraphs and 111In retention was shown to be long-lasting. Excretion was mainly seen during the first 24 hr after injection; thereafter whole-body retention remained stationary at 30%. Indium-111 activity in tumor biopsies and blood was measured using a gamma counter. Very high tumor-to-blood ratios were obtained: 150 for the primary tumor and 400-650 for liver metastases, which further justified radiation therapy. Indium-111-DTPA-D-Phe1-octreotide treatment was given on three separate occasions (3.0, 3.5 and 3.1 GBq) 8 and 4 wk apart. After each therapy, the patient experienced facial flush and pain over the skeletal lesions followed by symptomatic relief, even though no objective tumor regression was found radiologically after 5 mo. After initiation of octreotide treatment, there was a 14% reduction of the main tumor marker, urinary 5-HIAA. After three subsequent radionuclide therapies, there was a further 31% reduction of 5-HIAA levels. No adverse reactions, other than a slight decrease in leukocyte counts, were seen. The mean absorbed radiation dose after the three treatments was estimated to be about 10-12 Gy in liver metastases and 3-6 Gy in other tumors, depending on the size and location of the metastases. Assuming internalization of 111In into tumor cells and a radiobiological effect from short range Auger and conversion electrons, there might be a therapeutic effect on the tumor.
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| 54. |
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| 55. |
- Forssell-Aronsson, Eva, 1961, et al.
(författare)
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Advances in the diagnostic imaging of pheochromocytomas
- 2011
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Ingår i: Reports in Medical Imaging. - 1179-1586. ; 4, s. 19-37
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Forskningsöversikt (refereegranskat)abstract
- Pheochromocytomas (PCs) and paragangliomas (PGLs) are routinely localized by computed tomography (CT), magnetic resonance imaging (MRI), and metaiodobenzylguanidine (MIBG) scintigraphy. CT can identify tumors with high sensitivity but rather low specificity. MRI has higher sensitivity and specificity than CT and is superior to detect extra-adrenal disease. Radioiodinated MIBG scintigraphy has been used for more than 30 years and is based on MIBG uptake via the norepinephrine transporter on the cell membrane. The technique is very useful for whole-body studies in case of multiple primary tumors or metastases. Tumors with sole production of dopamine usually cannot be visualized with MIBG and may require positron emission tomographic (PET) studies with 18F-labeled radiotracers. Somatostatin receptor scintigraphy (SRS) using the radiolabeled somatostatin analog octreotide (based on the expression of the somatostatin receptors 2 and 5 by the tumor) can demonstrate PGL or metastases not visualized by MIBG. In this article, we review the use of MIBG scintigraphy to diagnose PC/PGL and compare the sensitivity and specificity with that of CT and MRI. We also describe the recent SRS and PET techniques and review the latest results of clinical studies by comparing these imaging modalities. Future perspectives of functional imaging modalities for PC/PGL are finally presented.
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| 56. |
- Forssell-Aronsson, Eva, 1961, et al.
(författare)
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Aspects on radionuclide therapy in malignant pheochromocytomas.
- 2006
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923. ; 1073, s. 498-504
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Tidskriftsartikel (refereegranskat)abstract
- Malignant pheochromocytomas/paragangliomas (PCs/PGs) often have distant metastases to the skeleton, liver, and lungs. Radionuclide therapy is valuable for treatment of disseminated tumor disease and could be used as adjuvant therapy after surgery. Patients with local and/or distant metastases of PC/PG should be investigated preoperatively by scintigraphy using both 123I-MIBG and 111In-DTPA-D-Phe1-octreotide, to evaluate the possibilities for radionuclide therapy (i.e., a dosimetric estimation of radiation dose to the tumor tissue versus critical normal tissues). Individual patient dose-planning should be performed. For patients in whom positive therapeutic effects are anticipated radionuclide therapy can be applied. Therapy with both 131I-MIBG and 177Lu-octreotate might be favorable in individual patients with lesions visualized by both metaiodobenzylguanidine (MIBG) and octreotide scintigraphy with enhanced therapeutic effects and reduced side effects.
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| 57. |
- Forssell-Aronsson, Eva, 1961, et al.
(författare)
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Biodistribution data from 100 patients i.v. injected with 111In-DTPA-D-Phe1-octreotide
- 2004
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 43:5, s. 436-42
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to obtain accurate data on the biodistribution of 111In-DTPA-D-Phe1-octreotide in tumour and normal tissues to facilitate dosimetric evaluations. Patients with carcinoid tumours, medullary thyroid carcinoma (MTC), differentiated thyroid tumours, endocrine pancreatic tumour (EPT), breast carcinoma, and various other tumour types were i.v. injected with 111In-DTPA-D-Phe-1-octreotide. Tumour and normal tissue samples were collected during surgery 1-35 days later, and the 111In activity concentration determined. Results showed large inter- and intra-individual variations. The 111In concentration was in general higher in carcinoids and some EPT (range 0.33-77% IA/kg) than in MTC and other tumours (0.017-7.8% IA/kg). Tumour-to-blood ratios (T/B) higher than 100 were found in most patients with carcinoids, EPT, renal carcinoma, and neuroendocrine carcinoma (max value 1500), while T/B was below 80 in most other tumours. Normal-tissue-to-blood ratios were in general < or = 10 but higher values were found in liver, kidneys, and spleen. The results presented are important for dosimetric calculations, when radiolabelled octreotide is used for diagnostic or therapeutic purposes.
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| 58. |
- Forssell-Aronsson, Eva, 1961, et al.
(författare)
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Indium-111 activity concentration in tissue samples after intravenous injection of indium-111-DTPA-D-Phe-1-octreotide.
- 1995
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 36:1, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- Indium-111 activity concentrations in human tumor and normal tissue samples were determined at 24, 48 and 120 hr after i.v. injection of 111In-DTPA-D-Phe-1-octreotide. Fourteen patients were included in the study. Seven patients had medullary thyroid carcinoma, four had midgut carcinoid tumors, two had endocrine pancreatic tumors and one had chronic pancreatitis.
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| 59. |
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| 60. |
- Forssell-Aronsson, Eva, 1961, et al.
(författare)
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Radionuclide therapy via SSTR - future aspects from experimental animal studies.
- 2013
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 97:1, s. 86-98
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Forskningsöversikt (refereegranskat)abstract
- There is need for better therapeutic options for neuroendocrine tumours. The aim of this review was to summarize results of experimental animal studies and raise ideas for future radionuclide therapy based on high expression of somatostatin (SS) receptors by many neuroendocrine tumours. In summary, one of the major options is individualized treatment for each patient, including choice of SS analogues, radionuclides and treatment schedules. Other options are methods to increase the treatment effect on tumour tissue (increasing tumour uptake and retention by upregulation of receptor expression and avoiding saturation of receptor binding), methods to increase the tumour tissue response (by choice of radionuclides, SS analogues or combined therapies), and methods to reduce side effects (diminished uptake and retention in critical organs and reduced normal tissue response). Furthermore, combination therapy with other radiopharmaceuticals, cytotoxic drugs or radiosensitizers can be considered to enhance the effects of radiolabelled SS analogues.
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